Prognostic Impact of Monosomal Karyotype in Patients with Myelodysplastic Syndrome and Abnormal Karyotype. A Report From the Spanish Group of MDS (GESMD)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1724-1724 ◽  
Author(s):  
David Valcárcel ◽  
Vera Adema ◽  
Mar Mallo ◽  
Margarita Ortega ◽  
Benet Nomdedeu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Risk Factor ◽  
Platelet Count ◽  
Statistical Significance ◽  
Refractory Anemia ◽  
Prognostic Impact ◽  
Abnormal Karyotype ◽  
Monosomal Karyotype

Abstract Abstract 1724 Cytogenetic abnormalities (CA) are the most important prognostic factor in patients with myelodysplastic syndromes (MDS). Monosomal karyotype (MK) defined as the presence of at least two autosomal monosomies or one monosomy plus other structural CA, has been associated with poor prognosis in acute myeloid leukemia (AML) but its significance in MDS remains unclear. The aim of our study was to analyze the prognostic impact of MK in adult patients with MDS and CA. Patients from Spanish Registry of MDS diagnosed with MDS by WHO 2008 criteria and with CA detected by conventional cytogenetics have been included in the study. Statistical analysis consisted of Kaplan-Meyer univariate analysis (UA) including all known variables associated with prognosis in MDS and a Cox-regression multivariate analysis (MA) in which we included only those variables with a P<0.1 in UA. There were 1054 patients, 478 (45.3%) women. The median age was 71 (range 16–96) years. Median follow-up for survivors was 24.1 (range 0–210) months. There were 609 (57,8%) refractory anemia (RA) and 445 (42.8%) refractory anemia with excess of blasts (RAEB). The IPSS was low, intermediate-1, intermediate-2 and high in 18.3%, 39.3%, 25%, and 10.6%, respectively (6.7% were unclassifiables). Complex karyotype (CK) and MK was observed in 203 (19.3%) and 172 (16.3%) patients, respectively. Patients with MK showed worse prognostic characteristics than those without MK: More Intermediate-2 and high risk patients (50% vs. 20% and 30% vs. 6.7%; P<0.001); more frequent CK: (87.2% vs. 6%; P<0.001), higher median bone marrow (BM) blast count (7% vs. 3%; P<0.001) and lower hemoglobin (Hb) level (89 vs. 96 g/L; P<0.001). Median OS for the whole group was 32.7 months. In the UA, the variables associated with lower OS were: Male sex, RAEB subtype (vs. RA), higher IPSS, CK, MK, older age, higher peripheral blood (PB) and bone marrow (BM) blast percentage and lower Hb, platelets and neutrophil count. In the MA the variables associated with lower OS were: Age>60 years (HR 1.7; P<0.001), CK (HR 2.19; P<0.001), higher BM blast (HR 1.07; P<0.001), Hb<100 g/L (HR 1.788; P<0.001) and platelet count <100×109/L (HR 1.62; p<0.001). MK did not reach statistical significance in the MA (HR 1.45; P=0.059). In the group of patients with CK the UA showed that the presence of MK was associated with a trend to lower OS (Log rank 2.8, P=0.092) while the presence of ≥4 vs. 3 CA was associated with lower OS (Log rank 7.5; P=0.006). Other variables associated with lower OS in UA in this subset of patients were: RAEB (vs RA), presence of abnormalities of 5 and/or 7 chromosome, higher IPSS group, older age, higher BM blast percentage, and lower Hb and platelet count. In MA the variables associated with lower OS in patients with CK were: age>60 years (HR 1.734, P=0.008), RAEB vs. RA (HR 1.542, P=0.02) Hb <100 g/L (HR 2.1, P<0.001) platelets <100×109/L (HR1.886; P=001) and the presence of abnormalities of both 5 and 7 chromosomes (HR 2.058; P=0.001). The presence of MK did not reach statistical significance in the MA. At last follow-up, 221(21%) patients had shown AML evolution at a median of 9 months (0–125 months) for a 1 and 4 years probability of AML evolution of 14.2% (95% CI 11.8–16.6) and 28.6% (95 CI: 24.8–32.4). The variables associated with higher risk of AML evolution in the UA were: RAEB, higher IPSS, CK, MK, higher PB and BM blast percentage and lower hemoglobin, platelet and neutrophil count. In multivariate analysis the only variables that retained statistical significance were BM blasts (HR 1.13; P<0.001) and CK (HR 3.2; P<0.001). In conclusion, our study shows that the presence of MK is highly associated with CK and other high-risk features of MDS. In our population, the MK was not an independent risk factor for OS while the presence of CK was the main risk factor associated with poorer OS in MDS patients with abnormal karyotype. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical Significance of Clonal Cytogenetic Heterogeneity (CCH) at Diagnosis in Adult Patients with Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2820-2820
Author(s):  
Hiroaki Shimizu ◽  
Nahoko Hatsumi ◽  
Satoru Takada ◽  
Takuma Ishizaki ◽  
Akihiko Yokohama ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Research Funding ◽  
Clonal Evolution ◽  
Statistical Significance ◽  
Prognostic Impact ◽  
Common Ancestry ◽  
Complex Karyotype ◽  
Abnormal Karyotype ◽  
Cytogenetic Abnormalities

Abstract Background:Although cytogenetic abnormalities at diagnosis are recognized as one of the most potent prognostic factors in acute leukemia patients, CCH acquisition at diagnosis, which are considered as a result of clonal evolution of leukemia cells, is not taken into account in prognostic classifications. Recent studies reported that CCH acquisition was observed in 24 - 32% of adult AML patients with abnormal karyotype, was more likely to occur in patients with older age and complex karyotype, and showed adverse prognostic impact. However, the clinical significance of CCH acquisition has not been investigated in adult ALL patients to date. Patients and methods: Of the 238 adult ALL patients diagnosed between 1990 and 2016, 120 patients with abnormal karyotype at diagnosis, who underwent intensive chemotherapy, were included in this study. CCH was defined as presence of two or more cytogenetically abnormal clones. A defined ancestral clonal evolution included either mother-daughter and/or branched patterns. In the mother-daughter pattern, a daughter clone showed all cytogenetic abnormalities of a mother clone plus additional abnormality(s), which define a distinct subclone. In a branch pattern, all subclones possessed common cytogenetic abnormalities suggesting presence of a common ancestry, but each subclone acquires unique additional abnormality(s), which define them as distinctive subclones. Both patterns of cytogenetic clonal evolution were sometimes seen in a patient. Composite karyotypes were applied to patients where a common ancestry could not be clearly determined because of too complicated cytogenetic findings. Fisher's exact test was used to compare binary variables. The logistic regression model was used for multivariate analysis of predisposing factors. Overall survival (OS) was estimated with the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazard model was used for multivariate analysis of prognostic factors. Values of p < 0.05 were considered to indicate statistical significance. Results:Of the 120 patients included in this study, 64 patients were male, and 56 were female. The median age was 50 years (range, 16-79 years). Karyotypes at diagnosis were Philadelphia chromosome (Ph) in 56 patients, complex in 15, and t(8;14) in seven. According to the definition described above, 47 patients (39%) showed CCH at diagnosis, and two (4%) among them were categorized as composite karyotype. Of the 45 patients harboring a defined ancestral clonal evolution, numbers of subclones were two, three, and four in 32 patients (68%), 11 (24%), and 2 (4%), respectively. Mother-daughter pattern, branched pattern, and both were seen in 34 patients (76%), 5 (11%), and 6 (13%). In univariate analysis for predisposing factors of CCH acquisition, only younger age was significantly associated with CCH acquisition (48% in age <= 50 vs. 29% in age > 50; p = 0.04), but not karyotype. This statistical significance was confirmed with multivariate analysis (odds ratio = 0.44; p = 0.03). When investigating the prognostic impact of CCH acquisition, patients were divided into Ph-negative or Ph-positive ALL groups. In the 64 Ph-negative ALL patients, the CR rates were not significantly different between patients with or without CCH (78% vs. 78%, respectively; p = 1.00). The OS rates were similar between two groups (26% vs. 39% at five years, respectively; p = 0.56). Multivariate analysis for OS revealed that complex karyotype and t(8;14) were independent prognostic factors, but not CCH acquisition. Likewise, in the 56 Ph-positive ALL patients, CCH acquisition was not significantly associated with the CR rates (92% vs. 78%, respectively; p = 0.27), and the OS rates did not significantly differ between the two groups (34% vs. 40% at five years, respectively; p = 0.90). In multivariate analysis for OS, no independent prognostic factor was identified. Conclusion: Adult ALL patients with abnormal karyotype acquired CCH at diagnosis with a frequency comparable to that of AML patients. However, unlike AML patients, CCH acquisition was more frequently observed in younger population and did not show any prognostic impact in ALL patients. These findings suggested that biological backgrounds of CCH acquisition at diagnosis were possibly different between in patients with ALL and AML. So, to confirm these important findings, clinical studies with larger study subjects are warranted. Disclosures Handa: Celgene: Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Prognostic and therapeutic impact of cytogenetic abnormalities in patients with myelodysplastic/myeloproliferative neoplasms, unclassifiable.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7058-7058
Author(s):  
Abhishek Avinash Mangaonkar ◽  
Hassan Alkhateeb ◽  
Aref Al-Kali ◽  
Naseema Gangat ◽  
Kebede Begna ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Treatment Guidelines ◽  
Myeloproliferative Neoplasms ◽  
Univariate Analysis ◽  
Prognostic Impact ◽  
Trisomy 8 ◽  
Abnormal Karyotype ◽  
Immature Myeloid Cells

7058 Background: The 2016 WHO classification includes myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U), as an MDS/MPN overlap syndrome not meeting criteria for well-defined entities such as CMML. No standard prognostication or treatment guidelines exist for such patients. Methods: We retrospectively identified MDS/MPN-U cases from 1990-2016 through our myeloid malignancies database. All bone marrow reports were reviewed to ensure compliance with 2016 WHO criteria. Clinical & cytogenetic parameters at diagnosis were assessed & compared with treatment outcomes. Results: Eighty nine patients met study criteria, with a median age of 69 years (range: 37-93); 58 (65%) males. Median follow-up was 22.2 months (range: 0-172), with 41 (46%) deaths & 13 (15%) leukemic transformations. Median OS was 24.8 months (range: 0-172). 43 (53%) patients had an abnormal karyotype, with common abnormalities being trisomy 8 (12%), complex karyotype (9%) & del (20q) (6%). Given the fewer types of abnormalities identified, the IPSS cytogenetic stratification was more effective than IPSS-R, with risk categorization including; 45 good (55%), 20 intermediate (25%) & 16 high risk (20%) respectively (8 unavailable). On univariate analysis, increased age (p = 0.05), decreased hemoglobin (p = 0.02), higher ANC (p = 0.03), circulating immature myeloid cells (p = 0.02), higher LDH (p = 0.009), absence of bone marrow ring sideroblasts (p = 0.001) & higher risk (intermediate & high) IPSS cytogenetic categories (p = 0.01) adversely impacted OS. In a multivariate model that included the aforementioned variables, higher risk IPSS cytogenetics retained a negative prognostic impact (p = 0.04). 28 patients received a median of 6 cycles (range: 1-21) of hypomethylating agent therapy (HMA), with an overall response rate of 18% (CR-3, PR-2). All responders had an abnormal karyotype (p = 0.01). However, HMA did not affect either OS or LFS. Conclusions: Intermediate & high risk IPSS cytogenetic categories independently & adversely impact survival in WHO defined MDS/MPN-U patients. HMA use did not impact OS; however, patients with abnormal karyotypes were more likely to respond.

scholarly journals Long-year follow-up of acute myocardial infarction with preserved initial LVEF: prognostic impact of progressively reduced LVEF

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Yoshioka ◽  
N Watanabe ◽  
Y Shibata ◽  
K Node
Keyword(s):  
Myocardial Infarction ◽  
Multivariate Analysis ◽  
Risk Factor ◽  
Acute Phase ◽  
Chronic Phase ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Prognostic Impact ◽  
Acute Mi

Abstract Background Severely reduced left ventricular ejection fraction (LVEF ≤35%) is commonly seen in approximately 5% of the myocardial infarction (MI) survivors in its acute-phase, which is recognized as a risk factor of post-MI cardiac death. However, clinical incidence and risk factor of the progressively reduced LVEF in the chronic-phase after MI has not been clarified. Purpose To evaluate clinical incidence and risk factor of the progressively reduced LVEF in the chronic-phase after MI by serial echocardiography. Method We evaluated 1144 consecutive patients with acute MI with preserved LVEF (≥50%) in acute-phase. Primary outcome was severely reduced LVEF (&lt;35%) in the chronic-pahse. We analyzed the predictive factor using multivariate analysis. Result During follow-up (median:1097 days), severely reduced LVEF newly developed in 8.6% of AMI survivors. Kaplan-meier curve is shown in the Figure. Multivariate analysis showed that men, eGFR &lt;30, AMI of LAD and absence of renin-angiotensin system blocking drugs was an independent predictor of severely reduced LVEF. Conclusions Progressively reduced LVEF during chronic-phase occurred 8.6% in acute MI survivors with preserved initial LVEF. Especially patients with these risk factors, careful long-term follow-up after MI should be needed to identify possible candidate for the implantable cardioverter-defibrillator. Figure 1 Funding Acknowledgement Type of funding source: None

Chromosomal and FISH Study of 286 Patients with Primary Myelofibrosis (PMF) Reveals Cryptic Abnormalities and Identifies Lesions Associated with Favorable Prognosis and Disease Progression,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3526-3526
Author(s):  
Vesna Najfeld ◽  
John Mascarenhas ◽  
Steven Fruchtman ◽  
Samuel Cytryn ◽  
Marina Kremyanskaya ◽  
...  
Keyword(s):  
Risk Factor ◽  
Disease Progression ◽  
Myeloproliferative Neoplasms ◽  
Normal Karyotype ◽  
Fusion Partner ◽  
Complex Karyotype ◽  
Wild Type ◽  
Abnormal Karyotype ◽  
Monosomal Karyotype

Abstract Abstract 3526 The pre-treatment karyotype is frequently a potent prognostic determinant of survival in patients (pts) with hematological malignancies. The prognostic significance of chromosomal aberrations, detected at time of diagnosis in pts with essential thrombocythemia (8–10%), polycythemia Vera (PV) (29%) and PMF (approximately 50%), is not well appreciated. We performed a retrospective analysis of 286 pts with PMF who had cytogenetic analyses at our single center between 1984 and July 2011. We first hypothesized that interphase FISH (I-FISH) studies might increase detection of chromosomal rearrangements. Initially, between 2000 and 2008 we performed I-FISH for the detection of the 5 most frequently rearranged loci in Ph negative myeloproliferative neoplasms and extended to 10 loci (1q21, EGR1 at 5q31, D7S511 at 7q31, P15/P16 at 9p21, ATM at 11q22.3, RB1 at 13q14, D20S108 at 20q11 and for numerical detection of chromosomes 7, 8, and 9) as of 2008. The addition of molecular cytogenetics revealed 146 pts (51%) with a normal karyotype and 140 (49%) with abnormal chromosomal lesions, including 12 pts with previously unrecognized lesions. To investigate the relationship between specific chromosomal lesions and JAK2V617F, testing when available after 2007, was performed in 170 of 286 (59%) pts. The V617F mutation was present in 66%. Wild type JAK2 (35%) PMF pts showed del(20q) (4 pts), del(13q) (3 pts), +8 (3 pts, one had cryptic +8), inv(12)(p11q15) (4pts), + der(19)t(1;19) (2pts), complex karyotype (2pts) as well as cryptic lesions (1pt)in a setting of a normal karyotype. The median follow up time of 31pts with normal baseline cytogenetics was 18 months (range 5 to 216 months) and 33% of these patients acquired an abnormal karyotype within the median time of 38mos (range 13–122 months). Four pts acquired a complex karyotype within the mean time of 13 mos (range 11–16 mos) while 2 pts acquired del(20q) within an average of 105 mos (126 and 84 mos). No patient developed a monosomal karyotype. Among 140 pts with an abnormal baseline karyotype, follow up studies were available for 29 pts. The median follow up time was 11 mos (range 5–93 mos) and clonal evolution was observed in 9 pts (31%). The most frequent recurrent abnormalities included del (20)(q11q13) in 30%, del(13q) in 18%, + 8 in 17%, +9/+9p in 16%, trisomy 1q/dup1q in 16%, and i(17q)/del(17p) in 9%. Complex karyotype involving 3 or more chromosomes was identified in 19% while monosomal karyotype, including loss of chromosomes 5, 6,7,17 and18 was observed in 11%. All 6 pts with +der(9)t(1;9)(q21;q12), had PV related PMF and 3 of these pts underwent allogeneic SCT, implying that this abnormality is associated with disease progression. A unique rearrangement, t(1;9) (p36;p24), resulted in identification of a novel JAK2 fusion partner. Survival of these pts based on their cytogenetic risk categories will be presented. Our observations demonstrated that a novel der(19)t(1;19) was detected only in JAK2V617F negative pts, while other abnormalities such as del(20q) and del(13q) are present in both mutation positive and wild type pts. These results confirm previous observations made by us and others that chromosomal abnormalities may occur either before or after JAK2V617F (Wang et al 2009). Even though 33% of pts will progress from a normal to an abnormal karyotype, monosomal karyotype does not appear to be a cytogenetic risk factor in these pts. The observation that the del(20q) abnormality developed over a 7–10 year period in pts with PMF, leads us to conclude that this specific cytogenetic abnormality should be considered a favorable prognostic risk factor. Disclosures: Off Label Use: Oral histone deacetylase inhibitor that targets epigenetic changes in malignant myelofibrosis cells with an goal to modify the disease process.

scholarly journals Height in Adolescence as a Risk Factor for Glioma Subtypes: a Nationwide Retrospective Cohort Study of 2.2 Million Subjects

2021 ◽  
Author(s):  
Roi Tschernichovsky ◽  
Lior H Katz ◽  
Estela Derazne ◽  
Matan Ben-Zion Berliner ◽  
Maya Simchoni ◽  
...  
Keyword(s):  
Risk Factor ◽  
Statistical Significance ◽  
Positive Association ◽  
High Grade Glioma ◽  
Low Grade ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Glioma Risk ◽  
Incident Cases

Abstract Background Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence. Methods The cohort included 2,223,168 adolescents between the ages of 16-19. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47,635,745 person-years. Cox proportional hazard models were used to estimate the hazard ratio for glioma and glioma subtypes according to height, body mass index (BMI) and sex. Results 1,195 patients were diagnosed with glioma during the study period. Mean(SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10cm increase) was positively associated with the risk for glioma of any type (HR 1.15; p=0.002). The association was retained in subgroup analyses for low-grade glioma (HR 1.17; p=0.031), high-grade glioma (HR 1.15; p=0.025), oligodendroglioma (HR 1.31; p=0.015), astrocytoma (HR 1.12; p=0.049), and a category of presumed IDH-mutated glioma (HR 1.17; p=0.013). There was a trend towards a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; p=0.07). After stratification of the cohort by sex, height remained a risk factor for men, but not for women. Conclusions The previously - established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype.

scholarly journals CNS Invasion in Meningioma—How the Intraoperative Assessment Can Improve the Prognostic Evaluation of Tumor Recurrence

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3620
Author(s):  
Felix Behling ◽  
Christina Fodi ◽  
Irina Gepfner-Tuma ◽  
Kathrin Machetanz ◽  
Mirjam Renovanz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Multivariate Analysis ◽  
Tumor Recurrence ◽  
Statistical Significance ◽  
Prognostic Impact ◽  
Central Nervous System Tissue ◽  
Intraoperative Assessment ◽  
Intraoperative Detection ◽  
The Central Nervous System

The detection of the infiltrative growth of meningiomas into CNS tissue has been integrated into the WHO classification as a stand-alone marker for atypical meningioma. However, its prognostic impact has been questioned. Infiltrative growth can also be detected intraoperatively. The prognostic impact of the intraoperative detection of the central nervous system tissue invasion of meningiomas was analyzed and compared to the histopathological assessment. The clinical data of 1517 cases with follow-up data regarding radiographic recurrence was collected. Histopathology and operative reports were reviewed and invasive growth was seen during resection in 23.7% (n = 345) while histopathology detected it in 4.8% (n = 73). The histopathological and intraoperative assessments were compatible in 63%. The prognostic impact of histopathological and intraoperative assessment was significant in the univariate but not in the multivariate analysis. Both methods of assessment combined reached statistical significance in the multivariate analysis (p = 0.0409). A score including all independent prognostic factors divided the cohort into three prognostic subgroups with a risk of recurrence of 33.8, 64.7 and 88.5%, respectively. The intraoperative detection of the infiltrative growth of primary meningiomas into the central nervous system tissue can complement the histopathological assessment of CNS invasion. The combined assessment is an independent prognostic factor regarding tumor recurrence and allows a risk-adapted tumor stratification.

Determination of Minimal Residual Disease in Patients with Acute Myeloid Leukemia by Multiparameter Flow Cytometry: Prognostic Impact at Different Checkpoints.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 400-400 ◽  
Author(s):  
Wolfgang Kern ◽  
Daniela Voskova ◽  
Claudia Schoch ◽  
Wolfgang Hiddemann ◽  
Susanne Schnittger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Residual Disease ◽  
Multiparameter Flow Cytometry ◽  
Prognostic Impact ◽  
Minimal Residual ◽  
Marrow Cells

Abstract Guiding antileukemic treatment in patients with acute myeloid leukemia (AML) is increasingly based on levels of minimal residual disease (MRD) which can be quantified with high sensitivity by multiparameter flow cytometry (MFC). The optimum checkpoint for determination of MRD during the course of therapy, however, has not yet been determined. We applied MFC using a comprehensive panel of antibodies to identify leukemia-associated aberrant immunophenotypes (LAIPs) at diagnosis and to quantify MRD by individually selected antibody combinations. The prognostic impact of MRD levels was assessed in comparison to cytogenetics and age. Patients received double induction, consolidation, and maintenance therapies and underwent allogeneic stem cell transplantation if they were younger than 60 years and had a matched related donor. In 286 patients with newly diagnosed and untreated AML MFC-based assessment for the presence of LAIP has been performed. The median percentage of LAIP-positive bone marrow cells at diagnosis was 16.04% (range, 2.54%–76.14%). All individual LAIPs were applied to 26 normal bone marrow samples to estimate sensitivity based on the median percentages of LAIP-positive normal bone marrow cells which ranged from 0.00% to 1.01% (median, 0.02%). A total of 550 follow-up samples has been analyzed in these patients at different checkpoints (CP1, up to day 21 after start of therapy, n=85; CP2, day 22–60, n=122; CP3, day 61–120, n=158; CP4, day 121–365, n=137; CP5, after day 365, n=48). In order to adjust for differences in the percentages of LAIP-positive bone marrow cells at diagnosis the logarithmic difference (LD) between diagnosis and follow-up was calculated for each follow-up sample. The median LDs at the respective checkpoints were: CP1, 2.02; CP2, 2.29; CP3, 2.39; CP4, 2.53; and CP5, 2.81. Separation of patients according to the respective median LDs resulted in differences in event-free survival (EFS; CP1: 21.1 vs. 9.1 months, p=0.0711; CP2: 14.2 vs. 9.3 months, p=0.0095; CP3: 30.9 vs. 13.5 months, p=0.0055; CP4: median not reached vs. 14.1 months, p<0.0001; CP5: median not reached vs. 22.5 months, p=0.0001) and overall survival (OS; CP3: median not reached vs. 21.6 months, p=0.0332; CP4: 90% vs. 53% at 2 years, p=0.0058). Cox analysis using the LDs at the different checkpoints as continuous variables confirmed the prognostic impact on EFS (CP2, p=0.002; CP3, p=0.0003; CP4, p<0.0001; CP5, p<0.0001) and revealed an impact also on OS (CP3, p=0.003; CP4, p=0.001; CP5, p=0.029). Cox regression analysis taking into consideration cytogenetics and age as covariates proved the independent prognostic impact of LD at checkpoints 2 to 5 on both EFS and OS with the exception of LD at checkpoint 2 and OS. In fact, LD at checkpoint 5 was the only parameter independently related to EFS and OS. These data suggest that quantification of MRD by MFC in AML results in powerful and independent prognostic parameters. In particular during the first year of treatment MRD levels provide important prognostic information. Clincal trials should use MRD-based stratification in order to assess the efficacy of early treatment intensification in high-risk AML patients.

Clonality in Granulocytes Detected by an Improved HUMARA Assay: A Good Prognostic Marker in Bone Marrow Failure Patients Exhibiting Chromosomal Abnormalities of Indefinite Significance.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3702-3702
Author(s):  
Ken Ishiyama ◽  
Chiharu Sugimori ◽  
Hirohito Yamazaki ◽  
Akiyoshi Takami ◽  
Shinji Nakao
Keyword(s):  
Bone Marrow ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Failure ◽  
Bone Marrow Examination ◽  
Refractory Anemia ◽  
Clonal Population ◽  
Dividing Cells ◽  
Humara Assay

Abstract Some patients with aplastic anemia (AA) and approximately 40% of patients with refractory anemia (RA) of myelodysplastic syndrome exhibit karyotypic abnormalities in bone marrow dividing cells. Although some of the patients undergo evolution to acute myeloid leukemia (AML), others follow a clinical course similar to AA patients without chromosomal abnormalities. Except for several abnormalities such as −7 and 5q-, the clinical significance of such chromosomal abnormalities in bone marrow failure patients remains unclear. We recently developed a reliable HUMARA assay capable of detecting a clonal population in granulocytes which constitutes 30% or more of total granulocytes (Blood. 2003;102:1211–1216). Studying correlation between chromosomal abnormalities and the presence of clonality may help in understanding the pathogenetic role of chromosomal abnormalities in AA and RA. We thus analyzed 50 acquired AA and 28 RA female patients who were heterozygous for the HUMARA gene. Chromosomal abnormalities such as add(5)(q13), 9q–9q+ and del(7)(q14q22) were found in 8% of AA and 21% of RA patients. Clonality was detected in 38% of AA patients and 39% of RA patients. Incidence of chromosomal abnormalities in patients with clonality (27%) was higher than that in patients without clonality (4%, p<0.01). In two AA patients who respectively exhibited add(5)(q13) in 10% and +8 in 38% dividing cells, clonality was not detected and these abnormal clones became undetectable at the time of subsequent bone marrow examination. Clonality was detected in the other 2 AA patients respectively exhibiting 9q–9q+ in 40% and del(7)(q14q22) in 25% dividing cells, and in all 5 RA patients respectively exhibiting +8 in 10%, del(5)(q13q31), dup(1)(q32q12) in 90%, del(5)(q13), add(11)(q23), inv(9) in 65% and X,-X in 100% of dividing cells. None of the 50 AA patients including 2 patients with clonality and chromosomal abnormalities underwent evolution to AML during 2-year follow up while one of 28 RA patients who exhibited del(5)(q13q31) progressed to AML. The proportion of clonal granulocytes in total granulocytes estimated by the HUMARA assay remained unchanged in most patients with clonality except for the transformed one. These data indicate that the chromosomal abnormality in bone marrow dividing cells is not necessarily associated with presence of clonal granulocyte population in peripheral blood and that detection of clonality in granulcytes in bone marrow failure patients with chromosomal abnormalities of indefinite significance is useful in predicting prognosis of these patients.

Chronic Myelomonocytic Leukemia (CMML) with More Than 15% of Ring Sideroblasts in Bone Marrow: An Overlapping Disorder Between CMML and Refractory Anemia with Ring Sideroblasts.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 290-290 ◽  
Author(s):  
Esperanza Such ◽  
Leonor Senent ◽  
Benet Nomdedeu ◽  
Javier Bueno ◽  
Teresa Bernal ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Who Classification ◽  
Multivariate Analyses ◽  
Lower Proportion ◽  
Chronic Myelomonocytic Leukemia ◽  
Refractory Anemia ◽  
Monocyte Count ◽  
Ring Sideroblasts ◽  
Myelomonocytic Leukemia

Abstract Abstract 290 The main diagnostic criteria for chronic myelomonocytic leukemia (CMML), a heterogeneous disorder sharing features of myelodysplastic syndromes (MDS) and chronic myeloproliferative disorders, is the existence of a sustained absolute monocyte count in peripheral blood (PB) above 1 × 109/L. On the other hand, the presence of more than 15% ring sideroblasts (RS) in bone marrow (BM) is a well recognized morphological feature of dyserithropoiesis and, in the absence of blasts in PB and less than 5% blasts in BM, is diagnostic of refractory anemia with ring sideroblasts (RARS) with or without multilineage dysplasia. In FAB as well as in WHO classification systems for myeloid neoplasms those cases presenting with both an absolute monocyte count in PB above 1 × 109/L and more than 15% RS in BM are diagnosed of CMML but the preeminence given to the monocyte count in PB over the proportion of RS in BM is not evidence-based. The main purpose of this study was to assess the clinical and biological characteristics and outcome [overall survival (OS) and acute leukemic (AL) evolution] of a series of 77 patients diagnosed of CMML by FAB and WHO criteria who had more than 15% RS in BM at presentation (CMML-RS) and to compare them with those of a series of 417 patients with CMML with less than 15% RS (classical CMML) and those of a series of 178 patients with classical RARS (38 patients with and 140 patients without multilineage dysplasia). Comparisons of proportions and ranks of variables between different groups were performed by chi square or Mann-Whitney-U tests as appropriate. Actuarial curves of OS and risk of AL evolution were built by Kaplan-Meier method and differences between curves compared with log-rank tests. Multivariate analyses of OS and risk of AL evolution were performed by Cox proportional hazards regression method. Patients with CMML-RS had lower hemoglobin level (P=0.008), lower absolute counts of leukocytes (P<0.001), neutrophils (P=0.002), and monocytes (P<0.001), higher platelet count (P<0.001), lower proportion of blasts in PB (P=0.015) and BM (P=0.035), and higher serum level of ferritin (P<0.001) and LDH (P=0.06) than patients with classical CMML. Patients with CMML-RS had significantly better OS than patients with classical CMML (median, 79 mo and 26 mo respectively; P<0.001; Figure) as well as lower risk of AL evolution (cumulative proportion at 5 yr, 7% and 20% respectively; P=0.07). Further, the beneficial prognostic relevance of the proportion of RS in BM on OS was maintained in multivariate analyses (P<0.001). In marked contrast, OS (median, 64 mo; Figure) and risk of AL evolution (cumulative proportion at 5 yr, 9%) of patients with classical RARS were closely similar to those observed in patients with CMML-RS (P>0.90). Patients with classical RARS were more anemic (P=0.001), had lower absolute counts of leukocytes (P<0.001), neutrophils (P=0.01), and monocytes (P<0.001), higher platelet count (P=0.002), lower proportion of blasts in PB (P=0.01) and BM (P<0.001), and lower serum level of ferritin (P=0.01) and LDH (P=0.11) than patients with CMML-RS. To avoid the potential interference in the analyses of disparities in the proportion of blasts in BM in the different groups of patients all the analyses were repeated excluding from all the groups those cases with 5% or more blasts in BM. Fifty-three patients with CMML-RS, 245 with classical CMML, and all 178 with classical RARS were evaluable for these sub-analyses. The results obtained were similar to those in the overall series of patients (data not showed). To sum up, all these results show that the proportion of RS in BM is a much powerful prognostic indicator than absolute monocyte count in PB in CMML and demonstrate that the presence of a proportion of RS greater than 15% in BM in patients with CMML defines a subset of patients that clearly differ in their biological characteristics from classical CMML and classical RARS. CMML-RS has a clinical course very close to that of classical RARS and markedly better than classical CMML. These data strongly suggest that CMML-RS is an overlapping syndrome between CMML and RARS. For clinical purposes patients with >1 × 109 monocytes/L in PB and >15% RS in BM should be better classified as RARS than as CMML. The WHO classification needs to be revisited to account for those findings. Disclosures: No relevant conflicts of interest to declare.

Incidence, Temporal Trends, and Predictors of Thrombocytopenia Among HIV-Infected Persons Treated with Combined Antiretroviral Therapy (cART)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 69-69
Author(s):  
Michele Bibas ◽  
Maria Paola Trotta ◽  
Patrizia Lorenzini ◽  
Alessandro Cozzi-Lepri ◽  
Antonella Castagna ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Antiretroviral Therapy ◽  
Incidence Rate ◽  
Drug Class ◽  
Hcv Infection ◽  
Cd4 Count ◽  
Hiv Replication ◽  
Hiv Rna

Abstract Abstract 69 Background: Thrombocytopenia (TP) is a relatively common disorder in HIV-infected Persons, and may be a challenging illness to treat, mainly because of its multifactorial aetiology. The underlying pathophysiology includes accelerated immune-mediated peripheral PLT destruction and impaired PLT production by the infected megakaryocytes of the bone marrow. Moreover, TP can also occur as a secondary phenomenon in HIV-positive patients, due to hypersplenism, bone marrow infiltration from infections of lymphoma, or myelosuppressive effects of medications. However, the epidemiology and predictors of TP in the era of potent HIV antiretroviral therapy has not been well defined. In a recent retrospective-matched case–control study of HIV-infected adult outpatients with (n=73) and without (n=73) TP, authors found that TP was significantly associated with HCV infection, cirrhosis, and uncontrolled HIV replication (Marks KM et al. J AIDS 2009). Antiretroviral therapy interruption among patients with well-controlled HIV infection has been associated with an increased incidence of thrombocytopenia, especially among those with a low baseline platelet count or a history of HIV-related thrombocytopenia (Bouldouyre MA et al. J AIDS 2009). Methods: The study was carried out in the Icona Foundation Study Cohort. All previously naïve starting cART with normal value of platelet count (PC) were included. TP has been defined as PC <100 × 109/L persisting in at least 2 consecutive determinations for at least 3 consecutive months. For each patient person-years of follow-up (PYFU) while receiving cART were calculated, and used to estimate the incidence rate of TP. A multivariable Poisson model was performed to elucidate the contribution of HIV viremia, immune reconstitution, HCV infection, ARV drug-class, and other potential risk factors for TP. Current HIV-RNA and CD4 count entered into the model as time-dependent covariates. Results: A total of 2,771 patients were included: 69.4% male, median age 36 yrs (IQR: 32–41), 38.5% HCV+. At initiation of cART, CD4 count and HIV-RNA were 295 cells/mmc and 4.75 log10 cp/mL, respectively. Mean value of baseline PC was 189 × 109/L (IQR 149–231). Overall patients contributed to 13,787 PYFU. During follow-up, 105 patients developed a TP accounting for an incidence rate of 7.6/1000 PYFU (95%CI 6.3–9.2). PC <20,000 was found in 5.7%, 20,000-50,000 in 12.4%, 50,000-100,000 in 81.4%. A trend for a reduction in the TP incidence rates over the last years was found (1997-1999: 9.8/1000 pyrs; 2000–2004: 4.6/1000 pyrs; 2005–2009: 4.5/1000 pyrs; P at Chi-square for temporal trend<0.001). At multivariable model, a higher risk of TP was associated with male gender (HR 1.99; 95%CI 1.19–3.32; P=0.008), and HCV co-infection (HR 3.45; 95%CI 2.23–5.33; P<0.001). Moreover, both lower level of current CD4 (HR 1.67 for 0–200 vs >350 cell/mmc; 95%CI 1.02–2.64; P=0.039) and detectable HIV viremia (HR 1.47 for each log10 cp/ml increase; 95%CI 1.25–1.73; P<0.001) were significantly associated with TP onset. No association with ARV drug-class was found. Conclusions: Thrombocytopenia remains a relatively common disorder in the late HAART era, with an overall 7.6 * 1000 PYFU, even if a trend for a reduced incidence over the last years was observed. In a large unselected cohort of antiretroviral naïve starting treatment, HCV co-infection, cirrhosis at baseline, uncontrolled HIV replication and lower current CD4 count were all independent predictors of TP. Furthermore in our study, the association with HCV-infection was independent from cirrhosis suggesting that mechanisms other than advanced liver disease may play a role in HIV/HCV-coinfected patients. In this cohort of treated patients, we found a strong association of TP with uncontrolled HIV replication and lower current CD4, these findings confirm the benefit of antiretroviral therapy on HIV-related thrombocytopenia. ON BEHALF OF THE ICONA FOUNDATION STUDY GROUP Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document